This proposal is a request for funds to purchase a Maldi/ToF/ToF mass spectrometer (Ultraflex-III, Bruker Daltonics) to upgrade the Mass Spectrometry and Proteomics Core Facility at the University of Utah. The instrument will serve two primary purposes: 1) replacement of an old, low-performance Maldi/ToF instrument and 2) provide a significant performance upgrade and new MS/MS capabilities with the Maldi/ToF/ToF design. Twelve major users from the University of Utah with 28 active NIH-funded projects have been identified with current and future projects that ensure immediate and continued full-capacity long-term usage. There are about 35 to 40 additional minor users. The group of major users will utilize different capabilities of the Maldi/ToF/ToF instrument. Several major users will require MS/MS capability for their research projects, while many of the major users will benefit from high performance and high sensitivity for analysis of large biomolecules, such as polymers and intact proteins. MS/MS with either low-energy LID fragmentation or high- energy CID fragmentation will be utilized for different applications. For instance, some users need high-energy CID for studying sulfated disaccharides and sulfation patterns in proteoglycan molecules;other users require LID fragmentation to characterize complex structures of modified peptides. Research applications for the requested Maldi/ToF/ToF instrument are wide and diverse, including topics such as polymer investigations for drug delivery systems, intact receptor proteins, development of fluorogenic peptide probes, discovery of novel neuropeptides from venomous snails, the role of sulfation patterns in proteoglycans, and discovery of unknown protein metal/ligand complexes. The Maldi/ToF/ToF instrument will be housed in the MS Core Facility, a central mass spectrometry shared resource that has been in operation at the University of Utah for nearly 30 years. The MS Core is administered by the Institution within a well-structured Core Research Facilities framework, including Oversight and Advisory committees. There is very strong Institutional financial support for long-term utilization of the instrument, including service agreements and full-time PhD mass spectrometrists. The long-term impact to the University of Utah and regional institutions is bringing a technologically-advanced resource to the scientific and medical research community that will provide state-of-the-art mass spectrometry for many years and will stimulate new research projects. The analytical power of the Ultraflex-III Maldi/ToF/ToF instrument will play a major role in accelerating research in many areas, particularly polymer- based drug delivery systems and many small molecule structure characterization projects. PUBLIC HEALTH RELEVANCE: The requested Maldi/ToF/ToF instrument is a high-performance mass spectrometer that will provide a significant upgrade to the mass spectrometry capabilities of the Mass Spectrometry and Proteomics Core Facility at the University of Utah, a University shared resource. The instrument will replace an obsolete Maldi/ToF mass spectrometer and bring powerful technology to advance the research of potentially more than 100 NIH-funded investigators at the University of Utah and regional institutions. This state-of-the-art mass spectrometer will have a long-term impact to the University of Utah by bringing a technologically advanced resource to the scientific and medical community which will help investigators make new discoveries and stimulate innovate research ideas in areas such as: drug delivery systems through biopolymer research and discovery of new medical uses for novel neuropeptides from venomous snails. This mass spectrometer will play a major role in accelerating research and development for a broad range of biomedical applications for many years to come.